We will investigate the physiological significance of proteolytic modifications of liver Fructose 1,6-bisphosphatase (Fru-P2ase) in relation to gluconeogenesis. We will also try to elucidate the cellular mechanisms responsible for the increase in number and digestive activity of lysosomes. Specifically, we will explore, also by means of recombination experiments, the relationship between the removal of peptide fragments from the NH2-terminus of each subunit and some catalytic and regulatory properties of Fru-P2ase, such as, a) sensitivity to allosertic effectors, b) binding and dissociation constants for the various ligands, including histidine-metal chelate, c) pH optimum for activity. The studies on both primary and hyperactive lysosomes will proceed along the following lines: a) characterization and distribution within the lysosomal fractions of the Fru-P2ase converting activities, b) patterns of distribution of carboxypeptidases, aminopeptidases and endopeptidases, c) possible mechanisms (energy requirement?) favouring the entry of digestible proteins into the lysosomes, using differently digested Fru-P2ase as a marker. The experiments on human erythrocyte G6PD will be mainly focused on the binding of native and variously modified forms of NADP and NADPH to be explored through spectrofluorimetry and equilibrium dialysis. We will also try to isolate some of the apoenzyme-coenzyme complexes formed during catalysis.